The Force Beyond Genetics

 

By Katherine Peng

From humans, to wookies, to Jar Jar Binks. With over 20 million species in the Star Wars galaxy, one can assume that not even this fictional universe is exempt from the laws of evolution. A conversation on how diverse environments pushed them to look so strange (or like cute little ewoks!) through rare mutations would be a discussion of the “hard inheritance” of DNA sequences, but what about soft inheritance? Can the surrounding environment in one lifespan change DNA in ways that can be passed on to offspring?

You’re shaking your head thinking DUH..NO, as thoughts jump back to the image of that giraffe in your biology 101 textbook. Remember that a once accepted theory of evolution proposed by Jean-Baptiste Lamarck suggested that acquired traits were inherited (e.g. a giraffe constantly stretching it’s neck to reach tall trees will give birth to giraffes with longer necks)? We now know that this theory is preposterous. What if Yoda lost his favorite toe in battle and decided to procreate? Would all future Yodas be afflicted with the curse of having only 5 toes?

BUT WAIT. Lamarck might have been onto something after all! Molecular biology has found that environmental factors CAN affect DNA without altering the sequence, and that these changes can be passed on to future generations (though not often beneficially). Welcome to the field of epigenetics!

In all eukaryotic cells in ours and the Star Wars galaxy, DNA is packaged around histone proteins. This DNA can be methylated and/or the histones can be modified to silent gene expression. People nowadays are becoming increasingly interested in how environmental factors produce these epigenetic changes and affect disease patterns.Genome-wide epigenetic studies are more commonly done on identical twins, where differences between individuals must be environmental. While Luke and Leia Skywalker are fraternal twins, sharing ~50% of their genes as would regular siblings, they were separated at birth to be raised in different environments. So, let’s take a look at how they become more different than their genetics would have us believe.

STRESS

In 2004, researchers from McGill University discovered that early nurturing from rat mothers remove epigenetic repression of the glucocorticoid receptor gene in rat pups. Consequently, rats that were not well nurtured became more sensitive to stress as adults.

 

Though childhood scenes of Luke and Leia are basically nonexistant, we do know that Leia was adopted into a very loving royal family who could not have children of their own. Luke was adopted by his step-uncle and step-uncle’s wife. His step-uncle did not approve of his adventurous tendencies, which created tension.

VERDICT: Though both twins are at risk of higher stress responses due to Amidala’s likely depression during pregnancy, hints of a less nurturing environment suggest that Luke may be more sensitive to stress as an adult than Leia.

EXERCISE

The Swedes are on a role in this category. A recent Swedish study shows that 20 minutes of exercise can reverse DNA methylation of genes in muscle that show lowered expression in type 2 diabetes. Another shows that 6 months of exercise changed the methylation pattern of genes in fat cells implicated in the risk of developing obesity or diabetes.

While Luke is working the moisture farm in Tattoine and having adventures, Leia is a palace princess in Alderaan.

VERDICT: While it seems that both Luke and Leia are fit later on, Luke appeared more active as a child and may be at a lower risk for type 2 diabetes. Sorry Leia.

DIET

Bioactive food components (in tea, soybean, etc.) might beneficially reduce DNA hypermethylation of cancer associated genes. On the flip side, folate found in fresh produce is required for DNA methylation, and its deficiency in pregnant moms may cause disease or cancer in children. You are also what your father eats. A mouse study showed that a paternal low-protein diet created upregulation of lipid biosynthesis in offspring.

Unfortunately, there’s no real information out there on the diet of the Skywalkers so…

VERDICT: Inconclusive.

 

So what have we learned here today? Leia needs to ramp up her training, and Luke should control that anxiety before he becomes like his father. But really, epigenetic changes in twins aren’t too different until later in life so I guess it’s all speculation until Disney releases the first installment of the sequel trilogy.

The Evolution of the Cutest Creatures in Star Wars

 

By Chris Spencer and Brent Wells, PhD

Credit:  Mary Harrsch (Flickr).
Credit:
Mary Harrsch
(Flickr).

Being such a staple of science fiction, Star Wars contains creatures whose evolution ought to be explainable scientifically. So strap in, and come with us as we cast Darwin’s eye over four species from the Star Wars galaxy:

 

WOOKIEE

The only wookiee we saw in the original trilogy was the enigmatic Chewbacca, but fortunately enough, we were able to get a glimpse of an entire wookiee community in Revenge of the Sith. These powerfully built furry humanoids are an arboreal race from the planet Kashyyyk. Being tree dwellers, they are well adapted for climbing – having sharp grasping claws, and strong backs and calves. Their characteristic fur has evolved for two purposes: it can be any of a range of earthy brown colours for camouflage whilst hunting terrestrially, and it produces a water repellent oil for swimming. Their sharp teeth and keen sense of smell are hallmarks of a species evolved to be hunters.

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Credit: originalpozer (Flickr).
Credit: originalpozer (Flickr).

RANCOR

According to Wookieepedia, rancors are large, carnivorous reptomammals from the planet Dathomir. Before I move on, a reptomammal, as far as I can tell, is a warm-blooded, oviparous reptile. Rancors grow as tall as 8-10 meters with long, pronounced arms and hands and small, under grown legs, kind of like a reverse T. Rex. This massively unbalanced center of gravity would normally be an evolutionary conundrum, but as a reptomammal, it’s clear the rancor plays by nobody’s rules, including natures, just like Earth’s duck-billed Platypus.

The massive size and top heaviness of rancors can be attributed to the low gravity on Dathomir. Alternatively, their size may be a consequence of the rich, almost unending diet the planet provides or the fact that Rancors, unlike regular mammals, lay eggs; it has been suggested that vivipary could limit the size of land-dwelling mammals. One final factor that could have aided in the evolution of such a large predator is the temperate climate the rancor evolved in. An inverse correlation between temperature and body size has been seen in some warm-blooded mammals, maybe because of overheating issues, maybe as a secondary consequence of higher atmospheric CO2, which would lead to more plant food sources and therefore prey food sources. The rancor’s thick, reptilian skin, large claws and teeth, and powerful jaws are all traits that evolved to aid their predatory abilities and their sense of smell became keen to help them find mates.

Rancors give birth to two young at a time, like polar bears, and following their birth, the young are carried on the body (one clutching to its chest and one to its back) until the young reach maturity. This is no easy feat considering the young are up to three meters tall at birth – this is nearly 50% the size of the adult rancor. As an apex predator, we can assume the rancor hunts and therefore attacks its prey. It would also need to defend its kill from other rancor and top predators roaming Dathomir in search of a free meal. Therefore, we can hypothesize that the evolution of its unnaturally long arms came as a way to do battle while the equivalent of a five-year-old child is strapped to its chest. Without extra-long arms with which to work around the front child, the young would surely perish during the battle, preventing the inheritance of genetic information and fixation of traits in the wild population. By carrying double their own bodyweight around in children, rancors have also found a way to lower infant mortality in the species.

 

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Credit: Brendan (Flickr).
Credit: Brendan (Flickr).

TAUNTAUN

These furry bipeds were used on Hoth by the rebellion in the opening scenes of Empire. Living on an enormous snowball such as Hoth will necessitate adaptations not dissimilar to those displayed by polar bears, including being warm blooded (they are reptomammals not unlike the rancor) – as referenced by Han’s innovative use of the interior of a tauntaun. Their tridactyl feet are furry and with splayed toes to act like snowshoes, with claws to help gain purchase on icier terrain. They also have four nostrils serving to warm air before entering the lungs. The larger pair of nostrils can seal to keep snow out during periods of rest. One key aspect of tauntaun physiology is one shared by many arctic fish: anti-freeze in the bloodstream.

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YODA

Credit: Angelo Su (Flickr).
Credit: Angelo Su (Flickr).

Yoda belongs to a species of small, long-lived creatures with green skin. His longevity is a consequence of a calorically restricted diet and an incredibly slow metabolism, something his species evolved in conjunction with their short stature and slow movement. They live in the wet, dark swamps of an unnamed planet similar to Dagobah, where Yoda was later exiled. Their diet is composed primarily of swamp plants and small insects. Yoda’s species has evolved tough claws on their fingers for prying bark from trees in search of beetles and other insects. Their unusually large ears have evolved as a means to avoid capture by larger, carnivorous animals that would gladly have them for dinner. Hearing predators from a distance is particularly necessary given their slow speed. Their green skin was also evolved as a defensive mechanism to help avoid predation through camouflage; green is the perfect colour for blending in with the large ferns and aquatic plants of their home planet and the creatures of this species are all but invisible among the green swamp gases that persistently hang in the air. Do not confuse Yoda’s bursts of speed during battle with a common trait of all members of his species. He was a Jedi Master, which provided him with special skills. A skill he did not possess, however, was a mastery of the English language.

 

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Sizzling Papers of the Week – Dec 13

 

The Scizzle Team

I’m Melting!  Melting snow and ice underlie extreme summer weather

Extreme summer weather has been on the rise this decade, while snow cover and sea ice have been declining – but how these were connected has remained a mystery.  Now, by combining satellite observation of snow and ice cover with atmospheric data, researchers have been able to demonstrate an association between the shrinking cryosphere and changes in atmospheric circulation, including reduced high latitude winds, a shifted jet stream, and more.  Loss of sea ice appears to have a stronger effect, even though this occurs at a lesser rate than snow loss.

Extreme summer weather in northern mid-latitudes linked to a vanishing cryosphere, Tang, Q. Zhang, X. and Francis, J.A., Nature Climate Change. December 12 2013

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Immune cells beat brain tumors

In the brain, tumors are often spurred by brain tumor initiating cells or BTICs.  Now, there may be a way to help stop BTICs’ action.  When macrophages or microglia from non-glioma humans were applied to BTICs in culture, the immune cells induced the expression of genes that stop the cell cycle, thus halting the progression of BTICs – an effect that was not seen when immune cells from glioma patients were used.  This action of microglia was enhanced by amphotericin B (AmpB); daily administration of the drug prolonged the life of animals with BTICs and the drug helped glioma-derived immune cells act like their healthier counterparts in fighting the tumor initiator cells.

Therapeutic activation of macrophages and microglia to suppress brain tumor-initiating cells, Sarkar, S. et al., Nature Neuroscience. December 8 2013.

Want to stay on top of  macrophages beating BTICs? Create a feed for BTIC, macrophages and glioma.  And read more in out earlier blog post on How Tumors Prosper in the Brain.

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Did ancient lungs have one way signs?

It was long thoughts that unidirectional flow in the lungs was the purview of birds, specialized for the demands of flying; then crocodilians were found to share this trait, suggesting that this airflow pattern may be as old as the Triassic period when birds and crocodilians split.  Now, investigators have shown that the savannah monitor lizard (Varanus exanthematicus) also share a unidirectional lung system.  This finding suggest that either the monitor lizards evolve this system independently, or unidirectional airflow it been around far longer than scientists thought, hailing from the Palaeozoic era.

Unidirectional pulmonary airflow patterns in the savannah monitor lizard, Schachner, E.R., et al., Nature. December 11 2013

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Who would like to chaperone this misfolded protein?

Gene mutations can lead to misfolded proteins, but just because they weren’t folded correctly doesn’t mean they aren’t functional. What renders misfolded proteins useless is their mis-routing by the cell, as these usually get stuck in the ER. However, a paper published in PNAS this week offers a brilliant solution – pharmacoperones – small molecules that will enter the cell, “correct” the protein and make sure it’s routed correctly. Using this technique, the researchers were able to restore the function of a mutant gonadotropin releasing hormone receptor (GnRHR) and by doing so restored the ability of the mice to have offspring. If this new technique can work in people, it will open the door to curing diseases ranging from cystic fibrosis to Alzheimer’s disease.

Restoration of testis function in hypogonadotropic hypogonadal mice harboring a misfolded GnRHR mutant by pharmacoperone drug therapy. Janovick et al., PNAS. December 2013.

Want to know on advances using pharmacoperones? Create a feed for pharmacoperones and another feed for following the senior author of the study Conn P.M.

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Leafing through the Literature

Thalyana Smith-Vikos

Highlighting recently published articles in molecular biology, genetics, and other hot topics

Small Molecules Achieve Pluripotency

Hou et al. have reached uncharted territory in stem cell research: rather than achieving pluripotency using the well-established transcription factor cocktail or recent advances in somatic cell nuclear transfer, mouse somatic cells were reprogrammed to generate pluripotent stem cells with a frequency of 0.2% using a cocktail of seven small molecules. These reprogrammed cells, termed chemically induced pluripotent stem cells (CiPSCs), were shown to resemble embryonic stem cells (ESCs) based on gene expression and epigenetic profiling, which is not case for other types of iPSCs.

Tissue and Organ Generation from Pluripotency

Takebe et al. report the first case of successful generation of a three-dimensional vascularized organ  Continue reading “Leafing through the Literature”

Porpoise-ful Evolution

Sally Burn

[quote style=”boxed” float=”right”]The happiness of the bee and the dolphin is to exist. For man it is to know that and to wonder at it.  Jacques Yves Cousteau[/quote]   

Dolphins are an object of fascination to many of us, with their quirky “smiles” and apparently playful nature appealing to young and old alike. Human uses for these sea mammals have ranged from service in the US Navy, to controversial food item, to subject of hippy artwork and questionable tattoos. The things that intrigue us the most about these animals though are probably their intellectual skills and the fact that they are fully aquatic mammals. But how did a mammal end up adapted to and completely living in an aquatic environment? Continue reading “Porpoise-ful Evolution”

Turtle Power!

Nicole Crown

We often use the phrase “when pigs fly” to describe something that is extremely unlikely to happen.  But why is it so crazy that pigs could ever evolve wings?  In fact, why didn’t they evolve wings?

Maybe pigs never evolved wings because they couldn’t.  That is, there are developmental constrains on the basic body plan of pigs that prevent them from evolving wings.

This concept of developmental constraints occurs frequently in evolutionary and developmental biology.  Certain stages of development are non-negotiable; if development deviates too far from a given program, there are serious consequences for the organism.

On the other hand, there must be some breathing room in developmental programs so that organisms can evolve and adapt.

So, how has nature struck a balance between the need to stick closely to a developmental plan, but also allow for noise and fluctuation so that adaptation can occur?

Comparative studies of morphological data have led to an hourglass model of development in which the most constrained stages occur in mid-development when the basic body plan of an organism is established (called the phylotypic stage), whereas early and late stages are less constrained.  This theory has been most recently supported by molecular studies that show gene expression patterns are most conserved during mid-development.

In a huge collaborative effort, Wang and colleagues1 sequenced the genome and transciptome of two turtle species, the soft-shell turtle and the green sea turtle.  They were able to answer long standing questions about the evolutionary origins of turtles (they’re a sister group to crocodilians and birds), gain insight into the molecular mechanisms of unique turtle characteristics (they might live so long because of a gene with a role in antioxidative stress) and into how a turtle builds its shell (co-option of Wnt signaling normally used in limb bud formation).

But perhaps most pertinent here is their comparative analysis of turtle embryo development.  The authors’ previous studies made broad comparisons among vertebrates, sampling from different sub-taxa (for example, frogs vs. mouse) and they found that in this case, the most conserved stage was the vertebrate phylotypic stage.  In their present study, the authors asked what the most conserved stage of development is if the two organisms are both vertebrates and amniotes (a subtaxa of vertebrates).  Would it be the vertebrate or the amniote phylotypic period?

They compared gene expression in all developmental stages of the soft-shell turtle to all stages of the chicken embryo and found that the stage with the most shared gene expression corresponded to the vertebrate phylotypic stage, not the amniote.  They also found that turtle-specific expression of 223 genes begins after establishing the basic vertebrate body plan.

The authors’ findings suggest that, in the case of vertebrates, evolution is constrained by the developmental establishment of the vertebrate body plan, but that later developmental stages were fair game for natural selection to act on, ultimately ending up in morphological novelties like the turtle shell.  It would be interesting for the authors to expand their comparisons to other amniotes with unique morphological features to see if this pattern holds true.

  1. Want et al (2013). “The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan.” Nature Genetics 45:6. doi:10.1038/ng.2615

Further reading:

Irie, N. and S. Kuratani (2011). “Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.” Nature Communications 2. doi: 10.1038/ncomms124

Leafing through the Literature

Thalyana Smith-Vikos

Highlighting recently published articles in molecular biology, genetics, and other hot topics

Trusting Your Gut Microbiota

Changes in human gut microbiota have been linked to an increasing likelihood of developing metabolic diseases. Karlsson et al. sequenced the fecal metagenome of 145 European women with normal, impaired or diabetic glucose control. From these profiles, the researchers developed a mathematical model to identify cases of type 2 diabetes, and predicted an individual’s diabetes-like metabolism by applying the model to women with impaired glucose control. They also discriminated between metagenomic markers for type 2 diabetes in their European cohort compared to a recently published Chinese cohort. Continue reading “Leafing through the Literature”